This project is based on the hypotheses that: (i) Spin trapping techniques can be used to identify low density lipoproteins (LDL) derived radicals and the spin traps may inhibit the oxidative modification of LDL; (ii) Free radical lipid peroxidation damages LDL as well as target macrophages and endothelial cells; (iii) Target cells utilize glutathione dependent selenoperoxidase(s) to detoxify LDL-lipid hydroperoxides (LDL-LOOHs). Specific aims of the project are as follows: (i) Elucidate mechanisms of radical generation during LDL oxidation; (ii) Characterize lipid-derived radical intermediates; (iii) Study formation and enzymatic inactivation of LDL-LOOHs in non-cellular systems; and (iv) Study toxicity and selenoperoxidase mediated detoxification of LDL-derived LOOHs in cellular systems. Techniques to be used include: spin trapping, mass spectrometry, high performance liquid chromatography, and gel electrophoresis. This comprehensive investigation of the free radical aspects of LDL oxidation, together with the formation and metabolism of LOOH intermediates, is hoped to increase understanding of the chemistry of LDL oxidative modification.